PROJECT SUMMARY/ABSTRACT: PROJECT 1 VIEWING NATIVE AMERICAN CERVICAL CANCER DISPARITIES THROUGH THE LENS OF THE VAGINAL MICROBIOME In the U.S., approximately 12,900 cases of cervical cancer are diagnosed each year, and annual mortality exceeds 4,000. According to Indian Health Service data from 1999-2009, American Indian/Alaskan Native (AI/AN) women had approximately a two-fold higher incidence of cervical cancer and associated mortality rate than white women. This cervical cancer disparity is primarily attributed to a lack of screening and unequal access to healthcare; however, other factors such as a higher prevalence of high-risk Human Papillomavirus (hrHPV) in AI/AN women are likely contributors as well. Certain compositions of the vaginal microbiota (VMB), the microorganisms that colonize the vagina, have recently been implicated in the development of cervical cancer, and have been observed to differ between white women and Hispanic women, where cervical cancer rate disparities have also been reported. The goal of this proposal is to address the role of the VMB and inflammation in cervical cancer pathogenesis in AI/AN women. The central hypothesis is that the VMB functions as a key regulator of mucosal inflammation in the female reproductive tract (FRT) that could affect the development of precancerous lesions and progression to invasive disease. To test this hypothesis two specific aims will be addressed in a small pilot project involving 100 AI/AN women and 100 non-AI/AN controls (50 healthy women and 50 women with cervical dysplasia in each group). It is anticipated that the results of this study will provide the framework and preliminary evidence to support a larger project. In Aim 1, a culturally sensitive vaginal sample collection protocol for AI/AN women will be developed and implemented in collaboration with the Native Americans for Community Action (NACA) clinic in Flagstaff, AZ. Subsequently, in Aim 2 correlations will be calculated among the vaginal microbiome composition, host immune activity, HPV genotypes, and Lactobacillus abundances in AI/AN women and non-AI/AN women to better understand the relationship between these factors and cervical dysplasia and to explore for the first time whether differences exist in the VMB of AI/AN and non-AI/AN women. Impact: This study will also provide the context for training AI/AN students at Northern Arizona University, University of Arizona, and Arizona State University in cutting edge biomedical research, and will be a step toward bringing genomics-based health advances to AI/AN communities.